Cancer strikes millions of people every year. Currently, there are several ways of treating cancer. A successful treatment depends on many factors, including but not limited to the type of cancer, accessibility to the tumor, and to the progression of cancer in the body prior to start of the treatment. Two types of treatment are commonplace in treating cancer. The first is chemotherapy and the second is radiation therapy. Chemotherapy, which is defined as treatment of a disease by chemicals, generally operates by targeting cells that divide at a high rate. Rapid cell division is a characteristic of cancerous cells. In contrast to chemotherapy, radiation therapy, also referred to as radiotherapy, involves subjecting tumors to ionizing radiation. Treatment variables, e.g., dosage, duration, type of radiation therapy, depend on the type of tumor, the location of the tumor, how far the tumor has progressed, and the health of the patient.
Cancerous cells have distinct properties that are different than normal cells. As cancer progresses in a patient, the cancerous cells require more nutrients and oxygen as compared to cells of surrounding normal tissues. As a result, cancerous cells require rapid proliferation of new blood vessel networks, also referred to as tumor angiogenesis, to keep up with increased demands for nutrition, oxygen, and removal of cellular waste products. While a normal vasculature is characterized by an organized branching pattern of arteries, veins, and capillaries, tumor vessels are highly disorganized, and endothelial cells therein, i.e., cells that line the interior surface of blood vessels, do not form regular monolayers. As a result, the endothelial cells do not have a normal barrier function. These abnormalities as well other abnormal vascular structures, known in the art, result in tumor blood vessel leakiness. The leakiness causes a high interstitial fluid pressure within the tumor which causes tumor blood vessels to collapse and thereby impede blood flow. The collapse of the blood vessels is one reason why tumor tissue is usually hypoxic, i.e., lower than normal oxygen concentration, even though it is highly vascularized.
Tumor hypoxia can fundamentally impact the successes of both radiation therapy and chemotherapy in a negative manner. Hypoxic cells are resistant to cell killing treatments, e.g. by ionizing radiation. For example, it is well established that hypoxic tumor cells are 2-3 times more radio-resistant than normoxic cells, i.e., cells with normal oxygen concentration. Since tumor hypoxia can negatively impact chemotherapy as well as radiation therapy, several methods have been proposed to reduce tumor hypoxia as well as methods that take advantage of tumor hypoxia for targeted treatments of cancer tumors.
One proposal is to use drugs that are activated under hypoxic condition to selectively target hypoxic cancer cells. This drug treatment is especially important to hypoxic cancer tumors that do not respond to a conventional dose of radiation or chemotherapy. Tirapazamine is an experimental drug that is activated to a toxic radical when introduced to a hypoxic environment. Tirapazamine initially produced effective results with tolerable toxicity in patients with advanced head and neck cancers. However, the clinical development of tirapazamine was recently terminated due to unexpected toxicity observed in an international pharmaceutical trial.
Another proposal is to reduce hypoxic regions of an expanding tumor by normalizing leaky tumor vasculature. The normalization of leaky tumor vasculature is accomplished by using anti-angiogenic agents that inhibit tumor growth by preventing new vessel formation. However, there is a paradox with using anti-angiogenic agents to normalize leaky tumor vasculature. It has been hypothesized that anti-angiogenic therapy blocks the growth of blood vessels. As a result, the anti-angiogenic therapy should not increase the efficacy of chemotherapy or radiation therapy since these treatments require functioning blood vessels for drug and/or oxygen delivery. Therefore, when administering anti-angiogenic therapy, a balance has to be reached between improving the vasculature of tumors to enable more efficient delivery of drug and oxygen, and inhibiting tumor growth by preventing new vessel formation. The balance can be reached by judiciously administering the anti-angiogenic compounds.
Another proposal is to increase oxygen concentration in the body. Tumor oxygenation can be influenced by the arterial oxygen supply to the tissue which depends on the arterial O2 and CO2 content, and tissue perfusion. Higher tumor oxygenation can be accomplished by asking patients to breathe high oxygen content gases, which have been shown to improve oxygenation in several human tumors. Another way of increasing tumor oxygen concentration is by placing the patient in a hyperbaric oxygen therapy. An exemplary hyperbaric oxygen therapy includes deliver of 100% (or nearly 100%) oxygen at greater than 1 atmosphere in a chamber that completely encapsulates the patient. However, these enhanced oxygen therapies decrease the heart rate while maintaining the same stroke volume, which results in decrease cardiac output. At the same time, these enhanced oxygen therapies increase after-load through systemic vasoconstriction. The two effects can cooperatively intensify congestive heart failure in some patients. Other side effects include high fever, asthma, seizures and claustrophobia.
Therefore, there is a need to increase oxygen concentration inside or near a cancer tumor that does not suffer from the side effects of the above mentioned therapies.